Lecture 8 Dr. Attya Bhatti Pedigree Analysis Lecture 8 Dr. Attya Bhatti

Pedigree A pictorial representation of a family history, essentially a family tree that outlines the inheritance of one or more characteristics.

Introduction: A “family tree,” drawn with standard genetic symbols, showing inheritance patterns for specific phenotypic characters is called pedigree. Analysis of inheritance pattern of phenotypic characters in a pedigree is called pedigree analysis. Propositus/Proband: A member of a family who first comes to the attention of a geneticist. The investigator then traces the history of the phenotype in the propositus back through the history of the family and draws a family tree, or pedigree.

Goals of Pedigree Analysis 1. Determine the mode of inheritance: dominant, recessive, partial dominance, sex-linked, autosomal, mitochondrial, maternal effect. 2. Determine the probability of an affected offspring for a given cross.

Basic Symbols

Generations labelled roman numerals I, II, ... Individuals labelled arabic numerals 1, 2, ...

Pedigree Analysis Males in a pedigree are represented by squares, females by circles. A horizontal line drawn between two symbols representing a man and a woman indicates a mating; children are connected to their parents by vertical lines extending below the parents. Persons who exhibit the trait of interest are represented by filled circles and squares. Unaffected persons are represented by open circles and squares. Each generation in a pedigree is identified by a Roman numeral; within each generation, family members are assigned Arabic numerals, and children in each family are listed in birth order from left to right. Deceased family members are indicated by a slash through the circle or square.

Autosomal recessive disorders The affected phenotype of an autosomal recessive disorder is determined by a recessive allele, and the corresponding unaffected phenotype is determined by a dominant allele. For example, the human disease phenylketonuria is inherited in a simple Mendelian manner as a recessive phenotype.

Autosomal recessive disorders The two key points are that generally the disease appears in the progeny of unaffected parents and the affected progeny include both males and females. When we know that both male and female progeny are affected, we can assume that we are dealing with simple Mendelian inheritance, not sex-linked inheritance.

Autosomal recessive disorders Fig: Pedigree of a rare recessive phenotype determined by a recessive allele.

Autosomal dominant disorders Here the normal allele is recessive, and the abnormal allele is dominant. A good example of a rare dominant phenotype with Mendelian inheritance is pseudo- achondroplasia, a type of dwarfism.

Autosomal dominant disorders Key points are, The main clues for identifying a dominant disorder with Mendelian inheritance are that the phenotype tends to appear in every generation of the pedigree and That affected fathers and mothers transmit the phenotype to both sons and daughters.

Autosomal dominant disorders Fig: Pedigree of a dominant phenotype determined by a dominant allele.

X-linked recessive disorders Phenotypes with X-linked recessive inheritance typically show the following patterns in pedigrees: 1.Many more males than females show the phenotype under study. This is because a female showing the phenotype can result only from a mating in which both the mother and the father bear the allele (for example, X A X a ×X a Y), whereas a male with the phenotype can be produced when only the mother carries the allele. If the recessive allele is very rare, almost all persons showing the phenotype are male.

X-linked recessive disorders 2. None of the offspring of an affected male are affected, but all his daughters are “carriers,” bearing the recessive allele masked in the heterozygous condition. Half of the sons of these carrier daughters are affected. 3. None of the sons of an affected male show the phenotype under study, nor will they pass the condition to their offspring. The reason behind this lack of male-to-male transmission is that a son obtains his Y chromosome from his father, so he cannot normally inherit the father’s X chromosome too.

X-linked recessive disorders Fig: Pedigree showing that X-linked recessive alleles expressed in males are then carried unexpressed by their daughters in the next generation, to be expressed again in their sons. Note that III-3 and III-4 cannot be distinguished phenotypically.

X-linked dominant disorders. These disorders have the following characteristics: 1.Affected males pass the condition to all their daughters but to none of their sons. 2.Affected heterozygous females married to unaffected males pass the condition to half their sons and daughters. One example is hypophosphatemia, a type of vitamin D-resistant rickets.

X-linked dominant disorders. Fig: Pedigree showing that all the daughters of a male expressing an X-linked dominant phenotype will show the phenotype.

X-linked dominant disorders. Fig: Pedigree showing that females affected by an X-linked dominant condition are usually heterozygous and pass the condition to half their sons and daughters